Diagnostic Value of Ultrasound Endoscopy-Guided Fine-Needle Aspiration for Peritoneal Lesions.

Background: Peritoneal lesions present diagnostic challenges, necessitating precise imaging techniques. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) offers a promising approach for accurate diagnosis, aiding in optimal patient management and treatment planning. Objective: This study aims to assess the diagnostic efficacy of EUS-FNA in peritoneal lesions to offer insight in guiding optimal patient management. Methods: A prospective observational study was conducted, and a total of 58 patients who underwent EUS-FNA of the peritoneum at our hospital between October 2021 and November 2021 were included. The ultrasound diagnostic instrument facilitated puncture guidance, with 2-5 punctures performed in various parts of the selected peritoneal lesion areas. The analysis encompassed evaluating the sensitivity, specificity, positive predictive value, and negative predictive value of biopsy for diagnosing peritoneal-associated lesions, alongside assessing the number of punctures, puncture satisfaction, and incidence of postoperative complications. Results: The included patients undergoing EUS-FNA revealed that 41 (70.69%) had malignant lesions, while 17 (29.31%) presented with benign lesions. The diagnostic accuracy of EUS-FNA for peritoneal lesions was determined to be 94.83%, with a diagnostic sensitivity of 97.30% for malignant tumors, specificity of 90.48%, positive predictive value of 94.74%, and negative predictive value of 95%. Lesions exhibited a size range of 2.5cm × 2.9cm to 15.2cm × 9.8cm. Each patient underwent 2-5 punctures (3.3 ± 1.4), with a puncture satisfaction rate of 96.55%. The incidence of postoperative complications following EUS-FNA was found to be 3.45%. Conclusion: EUS-FNA exhibits substantial diagnostic utility for peritoneal-related lesions, marked by exceptional accuracy, sensitivity, specificity, and favorable safety. Its clinical adoption is warranted, promising improved patient care and management.

Escin-induced DNA damage promotes escin-induced apoptosis in human colorectal cancer cells via p62 regulation of the ATM/γH2AX pathway.

Escin, a triterpene saponin isolated from horse chestnut seed, has been used to treat encephaledema, tissue swelling and chronic venous insufficiency. Recent studies show that escin induces cell cycle arrest, tumor proliferation inhibition and tumor cell apoptosis. But the relationship between escin-induced DNA damage and cell apoptosis in tumor cells remains unclear. In this study, we investigated whether and how escin-induced DNA damage contributed to escin-induced apoptosis in human colorectal cancer cells. Escin (5-80 µg/mL) dose-dependently inhibited the cell viability and colony formation in HCT116 and HCT8 cells. Escin treatment induced DNA damage, leading to p-ATM and γH2AX upregulation. Meanwhile, escin treatment increased the expression of p62, an adaptor protein, which played a crucial role in controlling cell survival and tumorigenesis, and had a protective effect against escin-induced DNA damage: knockdown of p62 apparently enhanced escin-induced DNA damage, whereas overexpression of p62 reduced escin-induced DNA damage. In addition, escin treatment induced concentration- and time-dependent apoptosis. Similarly, knockdown of p62 significantly increased escin-induced apoptosis in vitro and produced en escin-like antitumor effect in vivo. Overexpression of p62 decreased the rate of apoptosis. Further studies revealed that the functions of p62 in escin-induced DNA damage were associated with escin-induced apoptosis, and p62 knockdown combined with the ATM inhibitor KU55933 augmented escin-induced DNA damage and further increased escin-induced apoptosis. In conclusion, our results demonstrate that p62 regulates ATM/γH2AX pathway-mediated escin-induced DNA damage and apoptosis.

Quantum Oscillations in a Two-Dimensional Electron Gas at the Rocksalt/Zincblende Interface of PbTe/CdTe (111) Heterostructures.

Quantum oscillations are observed in the 2DEG system at the interface of novel heterostructures, PbTe/CdTe (111), with nearly identical lattice parameters (a(PbTe) = 0.6462 nm, a(CdTe) = 0.648 nm) but very different lattice structures (PbTe: rock salt, CdTe: zinc blende). The 2DEG formation mechanism, a mismatch in the bonding configurations of the valence electrons at the interface, is uniquely different from the other known 2DEG systems. The aberration-corrected scanning transmission electron microscope (AC-STEM) characterization indicates an abrupt interface without cation interdiffusion due to a large miscibility gap between the two constituent materials. Electronic transport measurements under magnetic field up to 60 T, with the observation of Landau level filling factor ν = 1, unambiguously reveal a π Berry phase, suggesting the Dirac Fermion nature of the 2DEG at the heterostructure interface, and the PbTe/CdTe heterostructure being a new candidate for 2D topological crystalline insulators.

Characterization of an abnormal photoluminescence behavior upon crystal-phase transition of perovskite CH3NH3PbI3.

Solution-processed hybrid perovskite of CH3NH3PbI3 (MAPbI3) exhibits an abnormal luminescence behavior at around the tetragonal-orthorhombic phase transition temperature. The combination of time resolved photoluminescence (PL), variable excitation power PL, and variable-temperature X-ray diffraction (XRD) allows us to clearly interpret the abnormal luminescence features in the phase transition region of MAPbI3. Both PL and XRD results unambiguously prove the coexistence of the tetragonal and orthorhombic phases of MAPbI3 in the temperature range of 150 to 130 K. The two luminescence features observed in the orthorhombic phase at T < 130 K originate from free excitons and donor-acceptor-pair (DAP) transitions, respectively. The comprehensive understanding of optical properties upon phase transition in MAPbI3 will benefit the development of new optoelectronic devices.

NLRP12 c.1382dup promotes the development of Crohn's disease through the ERK/NLRP3/ IL-1ß pathway.

Whole-genome sequencing was used to identify a dominant inherited NLRP12 c.1382dup mutation in refractory familial Crohn's disease (CD) patients. Additionally, we observed a T insertion at position 1382 in the third exon of NLRP12, leading to a frameshift mutation. Isolation of peripheral blood from mutation carriers and subsequent experiments demonstrated increased interleukin (IL)-1ß in CD patients with the NLRP12 c.1382dup mutation. However, the mechanisms by which the NLRP12 c.1382dup mutation mediates IL-1ß remain unclear. Our research findings reveal a close correlation between elevated p-ERK levels and increased expression of NLRP3 and IL-1ß in the presence of the NLRP12 c.1382dup mutation. Further experiments demonstrate that inhibiting p-ERK with PD98059 effectively reduces the production of NLRP3 and IL-1ß. This discovery provides new insights into the pathogenesis of CD, highlighting the significant role of the ERK/NLRP3/IL-1ß pathway in the progression of CD. Not only does this offer novel therapeutic targets for treating CD, but it also lays the groundwork for the development of treatment strategies targeting this pathway.

Replica symmetry breaking in 1D Rayleigh scattering system: theory and validations.

Spin glass theory, as a paradigm for describing disordered magnetic systems, constitutes a prominent subject of study within statistical physics. Replica symmetry breaking (RSB), as one of the pivotal concepts for the understanding of spin glass theory, means that under identical conditions, disordered systems can yield distinct states with nontrivial correlations. Random fiber laser (RFL) based on Rayleigh scattering (RS) is a complex disordered system, owing to the disorder and stochasticity of RS. In this work, for the first time, a precise theoretical model is elaborated for studying the photonic phase transition via the platform of RS-based RFL, in which we clearly reveal that, apart from the pump power, the photon phase variation in RFL is also an analogy to the temperature term in spin-glass phase transition, leading to a novel insight into the intrinsic mechanisms of photonic phase transition. In addition, based on this model and real-time high-fidelity detection spectral evolution, we theoretically predict and experimentally observe the mode-asymmetric characteristics of photonic phase transition in RS-based RFL. This finding contributes to a deeper understanding of the photonic RSB regime and the dynamics of RS-based RFL.

Identification of Gαi3 as a promising molecular oncotarget of pancreatic cancer.

The increasing mortality rate of pancreatic cancer globally necessitates the urgent identification for novel therapeutic targets. This study investigated the expression, functions, and mechanistic insight of G protein inhibitory subunit 3 (Gαi3) in pancreatic cancer. Bioinformatics analyses reveal that Gαi3 is overexpressed in human pancreatic cancer, correlating with poor prognosis, higher tumor grade, and advanced classification. Elevated Gαi3 levels are also confirmed in human pancreatic cancer tissues and primary/immortalized cancer cells. Gαi3 shRNA or knockout (KO) significantly reduced cell viability, proliferation, cell cycle progression, and mobility in primary/immortalized pancreatic cancer cells. Conversely, Gαi3 overexpression enhanced pancreatic cancer cell growth. RNA-sequencing and bioinformatics analyses of Gαi3-depleted cells indicated Gαi3's role in modulating the Akt-mTOR and PKA-Hippo-YAP pathways. Akt-S6 phosphorylation was decreased in Gαi3-depleted cells, but was increased with Gαi3 overexpression. Additionally, Gαi3 depletion elevated PKA activity and activated the Hippo pathway kinase LATS1/2, leading to YAP/TAZ inactivation, while Gαi3 overexpression exerted the opposite effects. There is an increased binding between Gαi3 promoter and the transcription factor TCF7L2 in pancreatic cancer tissues and cells. Gαi3 expression was significantly decreased following TCF7L2 silencing, but increased with TCF7L2 overexpression. In vivo, intratumoral injection of Gαi3 shRNA-expressing adeno-associated virus significantly inhibited subcutaneous pancreatic cancer xenografts growth in nude mice. A significant growth reduction was also observed in xenografts from Gαi3 knockout pancreatic cancer cells. Akt-mTOR inactivation and increased PKA activity coupled with YAP/TAZ inactivation were also detected in xenograft tumors upon Gαi3 depletion. Furthermore, bioinformatic analysis and multiplex immunohistochemistry (mIHC) staining on pancreatic cancer tissue microarrays showed a reduced proportion of M1-type macrophages and an increase in PD-L1 positive cells in Gαi3-high pancreatic cancer tissues. Collectively, these findings highlight Gαi3's critical role in promoting pancreatic cancer cell growth, potentially through the modulation of the Akt-mTOR and PKA-Hippo-YAP pathways and its influence on the immune landscape.

Identifying and evaluating a disulfidptosis-related gene signature to predict prognosis in colorectal adenocarcinoma patients.

Disulfidptosis, a regulated form of cell death, has been recently reported in cancers characterized by high SLC7A11 expression, including invasive breast carcinoma, lung adenocarcinoma, and hepatocellular carcinoma. However, its role in colon adenocarcinoma (COAD) has been infrequently discussed. In this study, we developed and validated a prognostic model based on 20 disulfidptosis-related genes (DRGs) using LASSO and Cox regression analyses. The robustness and practicality of this model were assessed via a nomogram. Subsequent correlation and enrichment analysis revealed a relationship between the risk score, several critical cancer-related biological processes, immune cell infiltration, and the expression of oncogenes and cell senescence-related genes. POU4F1, a significant component of our model, might function as an oncogene due to its upregulation in COAD tumors and its positive correlation with oncogene expression. In vitro assays demonstrated that POU4F1 knockdown noticeably decreased cell proliferation and migration but increased cell senescence in COAD cells. We further investigated the regulatory role of the DRG in disulfidptosis by culturing cells in a glucose-deprived medium. In summary, our research revealed and confirmed a DRG-based risk prediction model for COAD patients and verified the role of POU4F1 in promoting cell proliferation, migration, and disulfidptosis.

Carbon nanotubes encapsulating Pt/MoN heterostructures for superior hydrogen evolution.

Achieving efficient hydrogen evolution reaction (HER) catalysts to scale up electrochemical water splitting is desirable but remains a major challenge. Here, nitrogen-doped carbon nanotubes (NCNTs) loaded with PtNi/MoN electrocatalyst (PtNi/MoN@C) is synthesized by a simple strategy to obtain stronger interphase effects and significantly improve HER activity. The surface morphology of the materials is altered by Pt doping and the electronic structure of MoN is changed, which optimizing the electronic environment of the materials, shifting the binding energy and giving the materials a higher electrical conductivity, this ultimately leads to faster proton and electron transfer processes. The synergistic effect of Pt nanoparticles, MoN and the good combination with carbon leads to a high HER activity of 18 mV to reach 10 mA cm-2 in alkaline solution, outperforming that of the commercial Pt/C. Theoretical studies show that the heterostructures can efficiently enhance the electron transport and reduce the △GH*.

Comparative efficacy of different eating patterns in the management of type 2 diabetes and prediabetes: An arm-based Bayesian network meta-analysis.

AIMS/INTRODUCTION: Diet therapy is a vital approach to manage type 2 diabetes and prediabetes. However, the comparative efficacy of different eating patterns is not clear enough. We aimed to compare the efficacy of various eating patterns for glycemic control, anthropometrics, and serum lipid profiles in the management of type 2 diabetes and prediabetes. MATERIALS AND METHODS: We conducted a network meta-analysis using arm-based Bayesian methods and random effect models, and drew the conclusions using the partially contextualized framework. We searched twelve databases and yielded 9,534 related references, where 107 studies were eligible, comprising 8,909 participants. RESULTS: Eleven diets were evaluated for 14 outcomes. Caloric restriction was ranked as the best pattern for weight loss (SUCRA 86.8%) and waist circumference (82.2%), low-carbohydrate diets for body mass index (81.6%), and high-density lipoprotein (84.0%), and low-glycemic-index diets for total cholesterol (87.5%) and low-density lipoprotein (86.6%). Other interventions showed some superiorities, but were imprecise due to insufficient participants and needed further investigation. The attrition rates of interventions were similar. Meta-regression suggested that macronutrients, energy intake, and weight may modify outcomes differently. The evidence was of moderate-to-low quality, and 38.2% of the evidence items met the minimal clinically important differences. CONCLUSIONS: The selection and development of dietary strategies for diabetic/prediabetic patients should depend on their holistic conditions, i.e., serum lipid profiles, glucometabolic patterns, weight, and blood pressure. It is recommended to identify the most critical and urgent metabolic indicator to control for one specific patient, and then choose the most appropriate eating pattern accordingly.

Identification of matrix-remodeling associated 5 as a possible molecular oncotarget of pancreatic cancer.

Pancreatic cancer has an extremely poor prognosis. Here we examined expression, potential functions and underlying mechanisms of MXRA5 (matrix remodeling associated 5) in pancreatic cancer. Bioinformatics studies revealed that MXRA5 transcripts are significantly elevated in pancreatic cancer tissues, correlating with the poor overall survival, high T-stage, N1 and pathologic stage of the patients. MXRA5 mRNA and protein expression is significantly elevated in microarray pancreatic cancer tissues and different pancreatic cancer cells. In primary and immortalized (BxPC-3 and PANC-1 lines) pancreatic cancer cells, shRNA-induced MXRA5 silencing or CRISPR/Cas9-mediated MXRA5 knockout suppressed cell survival, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while provoking cell apoptosis. Conversely, forced overexpression of MXRA5 further promoted pancreatic cancer cell progression and EMT. Bioinformatics studies and the protein chip analyses revealed that differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in MXRA5-overexpressed primary pancreatic cancer cells were enriched in the PI3K-Akt-mTOR cascade. Indeed, Akt-mTOR activation in primary human pancreatic cancer cells was inhibited by MXRA5 shRNA or knockout, but was augmented following MXRA5 overexpression. In vivo, the growth of MXRA5 KO PANC-1 xenografts was largely inhibited in nude mice. Moreover, intratumoral injection of adeno-associated virus-packed MXRA5 shRNA potently inhibited primary pancreatic cancer cell growth in nude mice. Akt-mTOR activation was also largely inhibited in the MXRA5-depleted pancreatic cancer xenografts. Contrarily MXRA5 overexpression promoted primary pancreatic cancer cell growth in nude mice. Together, overexpressed MXRA5 is important for pancreatic cancer cell growth possibly through promoting EMT and Akt-mTOR activation. MXRA5 could be a potential therapeutic oncotarget for pancreatic cancer.

Protein glycosylation in urine as a biomarker of diseases.

Human body fluids have become an indispensable resource for clinical research, diagnosis and prognosis. Urine is widely used to discover disease-specific glycoprotein biomarkers because of its recurrently non-invasive collection and disease-indicating properties. While urine is an unstable fluid in that its composition changes with ingested nutrients and further as it is excreted through micturition, urinary proteins are more stable and their abnormal glycosylation is associated with diseases. It is known that aberrant glycosylation can define tumor malignancy and indicate disease initiation and progression. However, a thorough and translational survey of urinary glycosylation in diseases has not been performed. In this article, we evaluate the clinical applications of urine, introduce methods for urine glycosylation analysis, and discuss urine glycoprotein biomarkers. We emphasize the importance of mining urinary glycoproteins and searching for disease-specific glycosylation in various diseases (including cancer, neurodegenerative diseases, diabetes, and viral infections). With advances in mass spectrometry-based glycomics/glycoproteomics/glycopeptidomics, characterization of disease-specific glycosylation will optimistically lead to the discovery of disease-related urinary biomarkers with better sensitivity and specificity in the near future.

Cu-Based Multicomponent Metallic Compound Materials as Electrocatalyst for Water Splitting.

In this study, Cu-based multicomponent metallic compound materials M-Cu (M = Mn, Fe, Co, Ni, and Pt) were studied as electrocatalytic materials for water splitting. Different metal materials attached to the copper foam substrate can change the valence states of copper and oxygen, resulting in the change of electronic structure of the materials, thus changing its catalytic activity.

Insertion of carbon skeleton in Ni/MoO2 heterojunction with porous hollow sphere for efficient alkaline electrochemical hydrogen production.

The catalyst morphology has a strong impact on the activity of electrocatalytic hydrogen production. Considering the effect, we design and fabricate hollow spherical Ni/MoO2 heterojunction. In addition, an amorphous carbon skeleton is inserted into the hollow sphere, which makes the structure more stable and porous. Compared with other morphological Ni/MoO2, the porous hollow spherical Ni/MoO2 (H-Ni/MoO2) with an internal carbon skeleton shows better hydrogen evolution reaction (HER) activity with a small overpotential of 58 mV to reach 10 mA cm-2 and a tafel value of 44.8 mV dec-1 in alkaline media. The developed HER performance of H-Ni/MoO2 can be attributed to the larger active surface area of porous hollow spherical structure and the faster electron transfer and better stability of carbon skeleton. Undoubtedly, the urea plays a crucial role to construct the hollow spherical morphology and being decomposed to form holes and amorphous carbon in the synthesized steps. The soft-template strategy using urea as the addition for forming the porous hollow structure with carbon skeleton can be extended to explore superior non-noble metal for hydrogen production.

Octanoic acid-rich enteral nutrition prevented lipopolysaccharide-induced acute liver injury through c-Jun N-terminal kinase-dependent autophagy.

BACKGROUND: Acute liver injury (ALI) is an essential component of sepsis associated with poor outcomes. Octanoic acid (OA), a medium-chain fatty acid, has a protective effect on sepsis-induced organ damage, and autophagy is an adaptive response to sepsis. However, the underlying mechanism by which OA prevents ALI remains unknown. Therefore, we investigated whether OA-rich enteral nutrition (EN) prevented lipopolysaccharide (LPS)-induced ALI through the c-Jun N-terminal kinase (JNK)-dependent autophagy. METHODS: Firstly, Sprague Dawley rats were randomly divided into four groups (sham, LPS, LPS + EN, and LPS + EN + OA) to detect the effect of OA-rich EN on LPS-induced ALI. Then, rats were randomly divided into five groups (sham, LPS, LPS + EN + OA, LPS + EN + OA + anisomycin (AN), and LPS + SP600125) to explore the mechanism by which OA-rich EN prevented ALI. EN and OA-rich EN were conducted through gastric tubes for 3 days. The liver protective effects were measured by liver histopathological changes, enzymes, inflammatory cytokines of serum and liver, the levels of autophagy, and JNK activity. RESULTS: OA-rich EN inhibited JNK activity, up-regulated autophagy and prevented LPS-induced ALI. Inhibition of JNK activity conferred by SP promoted autophagy and prevented LPS-induced ALI. Moreover, the protective effect of autophagy and inhibition of JNK activity conferred by OA-rich EN on ALI was counteracted by AN. CONCLUSION: OA-rich EN prevented LPS-induced ALI through JNK-dependent autophagy. This result suggested that OA-rich EN may be a therapeutic potential for ALI in patients with sepsis.

Dysregulation and prometastatic function of glycosyltransferase C1GALT1 modulated by cHP1BP3/ miR-1-3p axis in bladder cancer.

BACKGROUND: Abnormal glycosylation in a variety of cancer types is involved in tumor progression and chemoresistance. Glycosyltransferase C1GALT1, the key enzyme in conversion of Tn antigen to T antigen, is involved in both physiological and pathological conditions. However, the mechanisms of C1GALT1 in enhancing oncogenic phenotypes and its regulatory effects via non-coding RNA are unclear. METHODS: Abnormal expression of C1GALT1 and its products T antigen in human bladder cancer (BLCA) were evaluated with BLCA tissue, plasma samples and cell lines. Effects of C1GALT1 on migratory ability and proliferation were assessed in YTS-1 cells by transwell, CCK8 and colony formation assay in vitro and by mouse subcutaneous xenograft and trans-splenic metastasis models in vivo. Dysregulated circular RNAs (circRNAs) and microRNAs (miRNAs) were profiled in 3 pairs of bladder cancer tissues by RNA-seq. Effects of miR-1-3p and cHP1BP3 (circRNA derived from HP1BP3) on modulating C1GALT1 expression were investigated by target prediction program, correlation analysis and luciferase reporter assay. Functional roles of miR-1-3p and cHP1BP3 on migratory ability and proliferation in BLCA were also investigated by in vitro and in vivo experiments. Additionally, glycoproteomic analysis was employed to identify the target glycoproteins of C1GALT1. RESULTS: In this study, we demonstrated upregulation of C1GALT1 and its product T antigen in BLCA. C1GALT1 silencing suppressed migratory ability and proliferation of BLCA YTS-1 cells in vitro and in vivo. Subsets of circRNAs and miRNAs were dysregulated in BLCA tissues. miR-1-3p, which is reduced in BLCA tissues, inhibited transcription of C1GALT1 by binding directly to its 3'-untranslated region (3'-UTR). miR-1-3p overexpression resulted in decreased migratory ability and proliferation of YTS-1 cells. cHP1BP3 was upregulated in BLCA tissues, and served as an miR-1-3p "sponge". cHP1BP3 was shown to modulate migratory ability, proliferation, and colony formation of YTS-1 cells, and displayed tumor-suppressing activity in BLCA. Target glycoproteins of C1GALT1, including integrins and MUC16, were identified. CONCLUSIONS: This study reveals the pro-metastatic and proliferative function of upregulated glycosyltransferase C1GLAT1, and provides preliminary data on mechanisms underlying dysregulation of C1GALT1 via miR-1-3p / cHP1BP3 axis in BLCA.

Study on the mechanism of LOXL1-AS1/miR-3614-5p/YY1 signal axis in the malignant phenotype regulation of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality worldwide. Accumulating researches have indicated that long non­coding RNAs (lncRNAs) are involved in varies human cancers, including HCC. Nevertheless, the specific molecular mechanism of lncRNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in HCC is still unclear. METHODS: LOXL1-AS1 expression was tested via qRT-PCR in HCC cells. Functional and mechanism assays were respectively done to evaluate the biological functions of HCC cells and the potential interaction of LOXL1-AS1 and other factors. RESULTS: We discovered that LOXL1-AS1 was high expressed in HCC cells. Inhibition of LOXL1-AS1 repressed cell proliferation, migration and invasion, but enhanced cell apoptosis in HCC. Further, miR-3614-5p was proven to be sponged by LOXL1-AS1. Additionally, Yin Yang 1 (YY1) was proven as the target gene of miR-3614-5p, and YY1 depletion could repress HCC cell malignant behaviors. YY1 could also transcriptionally activate LOXL1-AS1 expression. In rescue assays, we confirmed that overexpression of YY1 or miR-3614-5p inhibition could reverse the suppressive effects of LOXL1-AS1 silence on the malignant behaviors of HCC cells. CONCLUSION: In short, LOXL1-AS1/miR-3614-5p/YY1 forms a positive loop in modulating HCC cell malignant behaviors.

Exosome-Mediated Transfer of circ_0000338 Enhances 5-Fluorouracil Resistance in Colorectal Cancer through Regulating MicroRNA 217 (miR-217) and miR-485-3p.

Exosomes are microvesicles secreted by body cells for intercellular communication. The circular RNA circ_0000338 was found to be present in extracellular vesicles and improve the chemoresistance of colorectal cancer (CRC) cells. However, the role of exosomal circ_0000338 in 5-fluorouracil (5-FU) resistance in CRC is largely unknown. The levels of circ_0000338, microRNA 217 (miR-217), and miR-485-3p were detected using quantitative real-time PCR (qRT-PCR). The 50% inhibitory concentration (IC50) values of cells for 5-FU, cell proliferation, and apoptosis were evaluated using cell counting kit 8 (CCK-8), colony formation, flow cytometry, and Western blot assays. The interaction between miR-217 or miR-485-3p and circ_0000338 was confirmed by RNA immunoprecipitation (RIP), dual-luciferase reporter, and pulldown assays. Exosomes were isolated by ultracentrifugation and qualified by transmission electron microscopy (TEM), Nanosight tracking analysis (NTA), and Western blotting. Xenograft models were performed to analyze whether circ_0000338-loaded exosomes could increase resistance of CRC cells to 5-FU in vivo The circ_0000338 level was elevated in 5-FU-resistant CRC tissues and cells, and circ_0000338 knockdown sensitized 5-FU-resistant CRC cells to 5-FU through enhancing apoptosis and decreasing proliferation in vitro Mechanistically, circ_0000338 directly bound to miR-217 and miR-485-3p, and the inhibition of miR-217 or miR-485-3p reversed the effects of circ_0000338 knockdown on cell 5-FU resistance in CRC. Additionally, extracellular circ_0000338 could be incorporated into secreted exosomes and transmitted to 5-FU-sensitive cells. Treatment-sensitive cells with exosomes containing circ_0000338 reduced the 5-FU response in CRC both in vitro and in vivo Besides that, the exosomal circ_0000338 concentration was higher in patients exhibiting resistance to 5-FU and showed good diagnostic efficiency in 5-FU-resistant CRC. The delivery of circ_0000338 via exosomes enhanced 5-FU resistance in CRC through negative regulation of miR-217 and miR-485-3p, indicating a promising diagnostic and therapeutic marker for 5-FU-based chemotherapy in CRC patients.

Individualized prognostic signature for pancreatic carcinoma validated by integrating immune-related gene pairs (IRGPs).

Increasingly attention is being given to immune molecules in pancreatic cancer. The purpose of this study was to understand the potential clinical application of immune-regulated genes (IRGs) in the stratification of prognosis and to facilitate the development of personalized prognostic information for pancreatic cancer patients. We systematically used public data to comprehensively analyze immune-regulated gene pair (IRGP) expression profiles and clinical data. In our study, IRGP signature was identified to predict the overall survival (OS) of pancreatic cancer patients. We suggested that immune genes are enriched in different risk groups. In the high-risk group, M1 macrophages and resting NK cells were significantly enriched, while the percentages of naïve B cells, resting dendritic cells, CD8 T cells and regulatory T cells (Tregs) were significantly higher in the low-risk group, and we verified these results with immunohistochemical experiments. Gene ontology (GO) analysis confirmed that the IRGP index (IRGPI) signature genes in the cohort were mostly party to sensory perception of a chemical stimulus and the adaptive immune response. The identification of these pathways provides a basis for studying the molecular mechanisms of IRGPI signaling to predict the prognosis of pancreatic cancer. Our study effectively constructed a robust IRGP signature with prognostic value for pancreatic cancer, presenting a conceivable method for deciding on a preoperative treatment.

lncRNA NEAT1 facilitates the progression of colorectal cancer via the KDM5A/Cul4A and Wnt signaling pathway.

Colorectal cancer (CRC) is a major cause of cancer­related mortality. The aberrant expression of long non­coding RNAs (lncRNAs) is implicated in the pathogenesis of CRC. The present study investigated the role of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in CRC. lncRNA NEAT1 expression was detected in CRC tissues and cell lines. HCT116 cells were transfected with si­NEAT1, and the malignant behavior of the cells was detected. The binding associations between NEAT1 and E2F1, as well as between E2F1 and KDM5A were verified. si­NEAT1­transfected cells were also transfected with si­KDM5A. H3K4me3 methylation and cullin 4A (Cul4A) expression in HCT116 cells were detected. The si­NEAT1­transfected cells were also transfected with pc­Cul4A. Proteins related to the Wnt pathway were detected. A xenograft model of CRC using nude mice was established and the mice were injected with si­NEAT1­transfected HCT116 cells. lncRNA NEAT1 was found to be upregulated in CRC tissues and cells. NEAT1 silencing inhibited the malignant behaviors of the HCT116 cells. lncRNA NEAT1 inhibited KDM5A expression by binding to E2F1. The downregulation of KDM5A reversed the inhibitory effects of NEAT1 silencing on the malignant behavior of the cells. KDM5A inhibited Cul4A expression via the demethylation of H3K4me3. The overexpression of Cul4A promoted the malignant behavior of the si­NEAT1­transfected HCT116 cells. lncRNA NEAT1 activated the Wnt pathway via KDM5A/Cul4A. In vivo experiments confirmed the role of NEAT1 in CRC. On the whole, the present study demonstrates that lncRNA NEAT1 facilitates the progression of CRC via the KDM5A/Cul4A/Wnt axis.